Therapeutic approaches of ovarian CSCs Targeting CSCs might be a strategy to improve outcome of cancer patients but the complexities that lie within this approach will provide many challenges in clinical applications. Combined treatments AZD6244 order that target CSCs will be a new direction in the future. Some of these hurdles include overcoming the immune heterogeneity in CSC population as well as the

problem of epitopes shared with normal SCs and the necessity to identify additional CSCs antigens. Nevertheless, drug treatment for CSCs may increase the risk of toxicity since CSCs share common features with normal SCs. The current therapeutic strategies in ovarian CSCs are discussed below. Target therapy: cell surface markers Antibody therapies against tumor cell surface antigens have improved clinical prognosis through inhibition of specific signaling pathways, enhancing activation of direct immune effectors. In some cases, antibodies are conjugated with a bioactive drug that enables selective targeting of chemotherapeutic agents.

In other cases, they block a signaling pathway in which the marker may be involved. A monoclonal murine anti-human CD133 antibody conjugated to monomethyl-auristatin F (MMAF), a potential cytotoxic drug, has been shown to inhibit growth in hepatocellular and gastric cancer cells in vitro by inducing apoptosis [171]. Several antibodies against CD44v6 isoform have been developed and phase I clinical trials for patients suffering from head and neck squamous cell carcinoma Tucidinostat in vivo began with high hopes [20, 172]. CD44 is a surface adhesion molecule that binds to hyaluronic acid, which is related with tumor progression and metastasis. Hyaluronic acid bioconjugates Tangeritin with paclitaxel are being studied to enhance selective entry of cytotoxic drugs into human EOC cells expressing CD44 and for its use in intraperitoneal treatment of ovarian carcinoma [173]. SWA11, an antibody against CD24,reduced tumor size in xenograft mice transplanted by lung cancer cells A549 and

pancreatic cancer cells BxPC3 [174]. In 2009, Su and his colleagues successfully applied short hairpin RNA (shRNA) to reduce CD24 expression. The knockdown of CD24 decreased cell viability by in vitro activation of apoptosis in ovarian cell line SKOV3, also suppressing tumor growth in nude mice MK-8931 solubility dmso bearing ovarian cancer in vivo [175]. Therefore, CD24 inhibition may be considered as an effective approach for cancer therapy. Imatinib, a potent CD117 (c-KIT) specific inhibitor, has been used in clinical trials for the treatment of many types of cancer, including persistent epithelial ovarian cancer [176]. c-KIT is a receptor tyrosine kinase involved in cell signal transduction. It has been also suggested that CD117 in ovarian carcinoma was associated with poor response to chemotherapy. Therefore, c-KIT could be a perfecttherapeutic target of a tyrosine kinase inhibitor as imatinib.